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SIRT7 Facilitates CENP-A Nucleosome Assembly and Suppresses Intestinal Tumorigenesis
- Source :
- iScience, iScience, Vol 23, Iss 9, Pp 101461-(2020)
- Publication Year :
- 2020
- Publisher :
- Elsevier, 2020.
-
Abstract
- Summary SIRT7 is a member of the mammalian sirtuins and functions as an NAD+-dependent deacylase. Here we show that SIRT7 deficiency leads to a lowered histone acetyltransferase 1 (HAT1) activity and therefore decreased histone H4K5 and H4K12 acetylation. This in turn causes CENP-A dislocation at the centromere, which further affects chromatin assembly. SIRT7 ablation results in aneuploidy and aging phenotypes, including senescence and nucleolar expansion. Moreover, SIRT7 knockout mice are susceptible to DSS-induced colitis and alcohol-derived epithelial disturbance, revealing a disrupted intestinal epithelial homeostasis. Notably, absence of SIRT7 aggravates the susceptibility of colorectal cancer incidence in APCMin/+ mouse model and elicits further the Wnt signaling. Our findings indicate a tumor suppressive role of SIRT7 in the case of colorectal cancer. Together with the activities in maintaining genome integrity and intestinal homeostasis, activating SIRT7 may serve as a strategy to treat bowel diseases and colorectal cancer.<br />Graphical Abstract<br />Highlights • SIRT7 deacetylates HAT1 further regulates CENP-A nucleosome assembly • SIRT7 preserves genome integrity and intestinal homeostasis • SIRT7-ablation leads to intestinal tumorigenesis<br />Molecular Biology; Molecular Genetics; Cancer
- Subjects :
- 0301 basic medicine
Senescence
Nucleosome assembly
02 engineering and technology
Article
Molecular Genetics
03 medical and health sciences
medicine
lcsh:Science
Molecular Biology
Cancer
Multidisciplinary
biology
Wnt signaling pathway
Histone acetyltransferase
021001 nanoscience & nanotechnology
medicine.disease
Cell biology
030104 developmental biology
Histone
Knockout mouse
biology.protein
lcsh:Q
0210 nano-technology
HAT1
Subjects
Details
- Language :
- English
- ISSN :
- 25890042
- Volume :
- 23
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- iScience
- Accession number :
- edsair.doi.dedup.....1fbb58ec2b1292ce76971ab731d6f480